EHA 2023 | Insights into the future of AML therapy: the increasing use of targeted agents
Mark Levis, MD, PhD, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, shares his perspectives on the future of acute myeloid leukemia (AML) therapy. Dr Levis discusses the declining utilization of cytotoxic therapy due to the emergence of targeted agents and highlights the potential of menin inhibitors. Moreover, Dr Levis addresses the existing gaps in care, particularly for patients with spliceosome mutations exhibiting myelodysplastic syndrome (MDS) characteristics. Finally, Dr Levis sheds light on the changing role of allogeneic transplantation in the management of AML. This interview took place at the 28th Congress of the European Hematology Association (EHA) 2023 in Frankfurt, Germany.
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Transcript (edited for clarity)
I think the theme in the field is moving away from intensive therapy. Now that isn’t a view shared by all, but survival has gone up in the field in general when we have substituted targeted agents for the cytotoxic agents, and we are now in a position to really start decreasing the use of cytotoxic agents with the addition of specific targeted agents. So, we need to introduce more and more of these targeted agents...
I think the theme in the field is moving away from intensive therapy. Now that isn’t a view shared by all, but survival has gone up in the field in general when we have substituted targeted agents for the cytotoxic agents, and we are now in a position to really start decreasing the use of cytotoxic agents with the addition of specific targeted agents. So, we need to introduce more and more of these targeted agents. I think what we’re going to be occupied in doing for the next several years is learning who, and for whom, and how to use venetoclax in low intensity and high intensity regimens. But we need to continue to introduce new targeted agents – the next big category that I think are going to get approved are the menin inhibitors and those are looking to hit very specific subtypes of AML, that’s going to be the next quantum leap in the field, is menin inhibitors. And then the next targeted agent, no doubt. Every five years a new target is identified, and a drug effort is put forth – right now, it’s menin inhibitors, and you’re going to find that those probably apply to both NPM1 and MLL. The NPM1 is a large chunk of these “patients without a target”, so I think all of a sudden that’s going to change with menin inhibitors. And then you start mixing and matching, and you find perhaps venetoclax plus a menin inhibitor might work for yet another section. I think the last big group of patients that we really are lost on are the so called MDS signature patients, they have spliceosome mutations, ASXL1, that’s going to be the next breakthrough, but that I don’t see it yet, but I would anticipate it’s going to get druggable in the next decade, certainly if not much sooner.
I think you’re going to see less and less intensive chemotherapy, which is a very good thing. I don’t know that you’re going to see allogeneic transplant disappearing quite so soon, but that will be then the next object to make go away. We want to outlaw allogeneic transplant, we would like to eliminate the need for it, but right now we have not.
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